The major objective of this study is to shed light on the pathogenesis of CaEDTA toxicity. By so doing it is anticipated that approaches can be developed that would prevent toxicity when CaEDTA is used therapeutically (i.e. treatment of lead and certain radioactive metal poisonings) and/or establish a rational basis for corrective measures. For the coming year we plan to pursue two primary approaches using our basic animal model of infusing intravenously CaEDTA at 6 mmoles/kg/24 hours to rats. a) Effect on DNA metabolism: Determine how early DNA metabolism in the intestine is affected during the course of infusing CaEDTA. These data will be correlated with already established patterns of morphologic change (light and electron microscopy). b) comparative toxicity study of polyaminocarboxylic acid chelating agents. Chelators with higher affinity (CaDTPA, CaCDTA) and lower affinity (HoEDTA, EGTA) than EDTA for metals are being compared with respect to toxicity, urinary hydroxyproline and metal excretion, lysosomal enzyme activity and DNA metabolism. It is anticipated that these correlates will provide a clue as to the critical lesion in toxicity due to the polyaminocarboxylic acid chelating agents.